Adult Mesenchymal Stem Cells, Adult Neural Crest Stem Cells and Therapy of Neurological Pathologies: a State of Play

[en] Adult stem cells are endowed with in vitro multi-lineage differentiation abilities, and constitute an attractive autologous source of material for cell therapy in neurological disorders. With regards to lately published results, the ability of adult mesenchymal stem cells (MSC) and neural crest stem cells (NCSC) to integrate and differentiate into neurons once inside the central nervous system (CNS) is currently questioned. In this review, we collected exhaustive data on MSC/NCSC neural differentiation in vitro. We then analyzed pre-clinical cell therapy experiments in different models for neurological diseases and concluded that neural differentiation is probably not the leading property of adult MSC and NCSC concerning neurological pathologies management. Definitely, a fine analysis of the molecules that are secreted by MSC and NCSC would be of significant interest regarding their important contribution to the clinical and pathological recovery after CNS lesions.

Research Center/Unit :

Giga-Neurosciences - ULiège

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Neirinckx, Virginie ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Histologie

Coste, Cécile ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine

Rogister, Bernard ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine

Wislet, Sabine ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine

Language :

English

Title :

Adult Mesenchymal Stem Cells, Adult Neural Crest Stem Cells and Therapy of Neurological Pathologies: a State of Play

Publication date :

02 April 2013

Journal title :

Stem Cells Translational Medicine

ISSN :

2157-6564

eISSN :

2157-6580

Publisher :

Wiley-Blackwell, United Kingdom

Volume :

Issue :

Pages :

284-296

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 24 January 2013

Statistics

Number of views

87 (8 by ULiège)

Number of downloads

0 (0 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

Bibliography

Zhao, C, Deng W, Gage FH. Mechanisms and functional implications of adult neurogenesis. Cell 2008;132:645–660.
Hall, PA, Watt FM. Stem cells: The generation and maintenance of cellular diversity. Development 1989;106:619–633.
Thomson, JA, Itskovitz-Eldor J, Shapiro SS et al. Embryonic stem cell lines derived fromhuman blastocysts. Science 1998;282:1145–1147.
Takahashi, K, Tanabe K, Ohnuki M et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007;131:861–872.
Malgrange, B, Borgs L, Grobarczyk B et al. Using human pluripotent stem cells to untangle neurodegenerative disease mechanisms. Cell Mol Life Sci 2011;68:635–649.
Rice, CM, Scolding NJ. Autologous bone marrow stem cells: Properties and advantages. J Neurol Sci 2008;265:59–62.
Friedenstein, AJ, Deriglasova UF, Kulagina NN et al. Precursors for fibroblasts in different populations of hematopoietic cells as detected by the in vitro colony assay method. Exp Hematol 1974;2:83–92.
Bianco, P, Riminucci M, Kuznetsov S et al. Multipotential cells in the bone marrow stroma: Regulation in the context of organ physiology. Crit Rev Eukaryot Gene Expr 1999;9:159–173.
Uccelli, A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol 2008;8:726–736.
Caplan, AI, Correa D. The MSC: An injury drugstore. Cell Stem Cell 2011;9:11–15.
Sanchez-Ramos J, Song S, Cardozo-Pelaez F et al. Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol 2000;164:247–256.
Woodbury, D, Schwarz EJ, Prockop DJ et al. Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 2000;61:364–370.
Dominici, M, Le Blanc K, Mueller I et al. Minimal criteria for defining multipotent mesenchymal stromal cells: The International Society for Cellular Therapy position statement. Cytotherapy 2006;8:315–317.
Jiang, Y, Jahagirdar BN, Reinhardt RL et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002;418: 41–49.
Reyes, M, Lund T, Lenvik T et al. Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. Blood 2001;98:2615–2625.
D’Ippolito G, Diabira S, Howard GA et al. Marrow-isolated adult multilineage inducible (MIAMI) cells, a unique population of postnatal young and old human cells with extensive expansion and differentiation potential. J Cell Sci 2004;117:2971–2981.
D’Ippolito G, Howard GA, Roos BA et al. Isolation and characterization of marrow-isolated adult multilineage inducible (MIAMI) cells. Exp Hematol 2006;34:1608–1610.
Pittenger, MF, Mackay AM, Beck SC et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999;284:143–147.
Morrison, SJ, White PM, Zock C et al. Prospective identification, isolation by flow cytometry, and in vivo self-renewal of multipotent mammalian neural crest stem cells. Cell 1999;96:737–749.
Kruger, GM, Mosher JT, Bixby S et al. Neural crest stem cells persist in the adult gut but undergo changes in self-renewal, neuronal subtype potential, and factor responsiveness. Neuron 2002;35:657–669.
Toma, JG, McKenzie IA, Bagli D et al. Isolation and characterization of multipotent skin-derived precursors from human skin. STEM CELLS 2005;23:727–737.
Hu, YF, Zhang ZJ, Sieber-Blum M. An epidermal neural crest stem cell (EPI-NCSC) molecular signature. STEM CELLS 2006;24:2692–2702.
Nagoshi, N, Shibata S, Kubota Y et al. Ontogeny and multipotency of neural crest-derived stem cells in mouse bone marrow, dorsal root ganglia, and whisker pad. Cell Stem Cell 2008;2:392–403.
Yoshida, S, Shimmura S, Nagoshi N et al. Isolation of multipotent neural crest-derived stem cells from the adult mouse cornea. STEM CELLS 2006;24:2714–2722.
Tomita, Y, Matsumura K, Wakamatsu Y et al. Cardiac neural crest cells contribute to the dormant multipotent stem cell in the mammalian heart. J Cell Biol 2005;170:1135–1146.
Arthur, A, Rychkov G, Shi S et al. Adult human dental pulp stem cells differentiate toward functionally active neurons under appropriate environmental cues. STEM CELLS 2008;26: 1787–1795.
Widera, D, Zander C, Heidbreder M et al. Adult palatum as a novel source of neural crest-related stem cells. STEM CELLS 2009;27: 1899–1910.
Pardal, R, Ortega-Saenz P, Duran R et al. Glia-like stem cells sustain physiologic neurogenesis in the adult mammalian carotid body. Cell 2007;131:364–377.
Morikawa, S, Mabuchi Y, Niibe K et al. Development of mesenchymal stem cells partially originate from the neural crest. Biochem Biophys Res Commun 2009;379:1114–1119.
Laurent, LC, Ulitsky I, Slavin I et al. Dynamic changes in the copy number of pluripotency and cell proliferation genes in human ESCs and iPSCs during reprogramming and time in culture. Cell Stem Cell 2011;8: 106–118.
Bakhtiari, M, Mansouri K, Sadeghi Y et al. Proliferation and differentiation potential of cryopreserved human skin-derived precursors. Cell Prolif 2012;45:148–157.
Delcroix, GJ, Curtis KM, Schiller PC et al. EGF and bFGF pre-treatment enhances neural specification and the response to neuronal commitment of MIAMI cells. Differentiation 2010;80:213–227.
Curtis, KM, Gomez LA, Schiller PC. Rac1b regulates NT3-stimulated Mek-Erk signaling, directing marrow-isolated adult multilineage inducible (MIAMI) cells toward an early neuronal phenotype. Mol Cell Neurosci 2012;49: 138–148.
Jori, FP, Napolitano MA, Melone MA, et al. Molecular pathways involved in neural in vitro differentiation of marrow stromal stem cells. J Cell Biochem 2005;94:645–655.
Karaöz E, Demircan PC, Saglam O et al. Human dental pulp stem cells demonstrate better neural and epithelial stem cell properties than bone marrow-derived mesenchymal stem cells. Histochem Cell Biol 2011;136:455–473.
Kim, SS, Choi JM, Kim JW, et al. cAMP induces neuronal differentiation of mesenchymal stem cells via activation of extracellular signal-regulated kinase/MAPK. Neuroreport 2005;16:1357–1361.
Király M, Porcsalmy B, Pataki A et al. Simultaneous PKC and cAMP activation induces differentiation of human dental pulp stem cells into functionally active neurons. Neurochem Int 2009;55:323–332.
Kondo, T, Johnson SA, Yoder MC et al. Sonic hedgehog, retinoic acid synergistically promote sensory fate specification from bone marrow-derived pluripotent stem cells. Proc Natl Acad Sci USA 2005;102:4789–4794.
Kondo, T, Matsuoka AJ, Shimomura A et al. Wnt signaling promotes neuronal differentiation from mesenchymal stem cells through activation of Tlx 3. STEM CELLS 2011;29:836–846.
Lebonvallet, N, Boulais N, Le Gall C et al. Characterization of neurons from adult human skin-derived precursors in serum-free medium: A PCR array and immunocytological analysis. Exp Dermatol 2012;21:195–200.
Lepski, G, Jannes CE, Maciaczyk J et al. Limited Ca2+ and PKA-pathway dependent neurogenic differentiation of human adult mesenchymal stem cells as compared to fetal neuronal stem cells. Exp Cell Res 2010;316: 216–231.
Lim, JY, Park SI, Kim SM et al. Neural differentiation of brain-derived neurotrophic factor- expressing human umbilical cord blood-derived mesenchymal stem cells in culture via TrkB-mediated ERK and beta-catenin phosphorylation and following transplantation into the developing brain. Cell Transplant 2011;20: 1855–1866.
Lim, JY, Park SI, Oh JH et al. Brain-derived neurotrophic factor stimulates the neural differentiation of human umbilical cord blood-derived mesenchymal stem cells and survival of differentiated cells through MAPK/ERK and PI3K/Akt-dependent signaling pathways. J Neurosci Res 2008;86:2168–2178.
Lin, X, Zhang Y, Dong J et al. GM-CSF enhances neural differentiation of bone marrow stromal cells. Neuroreport 2007;18:1113–1117.
Liqing, Y, Jia G, Jiqing C et al. Directed differentiation of motor neuron cell-like cells from human adipose-derived stem cells in vitro. Neuroreport 2011;22:370–373.
Qi, Y, Zhang F, Song G et al. Cholinergic neuronal differentiation of bone marrow mesenchymal stem cells in rhesus monkeys. Sci China Life Sci 2010;53:573–580.
Rooney, GE, Howard L, O’Brien T et al. Elevation of cAMP in mesenchymal stem cells transiently upregulates neural markers rather than inducing neural differentiation. Stem Cells Dev 2009;18:387–398.
Scintu, F, Reali C, Pillai R et al. Differentiation of human bone marrow stem cells into cells with a neural phenotype: Diverse effects of two specific treatments. BMC Neurosci 2006;7:14.
Tatard, VM, D’Ippolito G, Diabira S et al. Neurotrophin-directed differentiation of human adult marrow stromal cells to dopaminergic- like neurons. Bone 2007;40:360–373.
Tio, M, Tan KH, Lee W et al. Roles of dbcAMP, IBMX and RA in aspects of neural differentiation of cord blood derived mesenchymallike stem cells. PLoS One 2010;5:e9398.
Trzaska, KA, Kuzhikandathil EV, Rameshwar P. Specification of a dopaminergic phenotype from adult human mesenchymal stem cells. STEM CELLS 2007;25:2797–2808.
Wang, TT, Tio M, Lee W et al. Neural differentiation of mesenchymal-like stem cells from cord blood is mediated by PKA. Biochem Biophys Res Commun 2007;357:1021–1027.
Wislet-Gendebien S, Laudet E, Neirinckx V et al. Mesenchymal stem cells and neural crest stem cells from adult bone marrow: Characterization of their surprising similarities and differences. Cell Mol Life Sci 2012;69:2593–2608.
Ying, C, Hu W, Cheng B et al. Neural differentiation of rat adipose-derived stem cells in vitro. Cell Mol Neurobiol 2012;32:1255–1263.
Zhang, L, Seitz LC, Abramczyk AM et al. cAMP initiates early phase neuron-like morphology changes and late phase neural differentiation in mesenchymal stem cells. Cell Mol Life Sci 2011;68:863–876.
Zhang, L, Tan X, Dong C et al. In vitro differentiation of human umbilical cord mesenchymal stem cells (hUCMSCs), derived from Wharton’s jelly, into choline acetyltransferase (ChAT)-positive cells. Int J Dev Neurosci 2012; 30:471–477.
Zhang, W, Zeng YS, Wang JM et al. Neurotrophin- 3 improves retinoic acid-induced neural differentiation of skin-derived precursors through a p75NTR-dependent signaling pathway. Neurosci Res 2009;64:170–176.
Bi, Y, Gong M, Zhang X et al. Pre-activation of retinoid signaling facilitates neuronal differentiation of mesenchymal stem cells. Dev Growth Differ 2010;52:419–431.
Foudah, D, Scuteri A, Redondo J et al. Evaluation of neural markers expression in human mesenchymal stem cells after mesengenic differentiation. Ital J Anat Embryol 2011; 116(suppl):16.
Tondreau, T, Lagneaux L, Dejeneffe M et al. Bone marrow-derived mesenchymal stem cells already express specific neural proteins before any differentiation. Differentiation 2004;72:319–326.
Montzka, K, Lassonczyk N, Tschoke B et al. Neural differentiation potential of human bone marrow-derived mesenchymal stromal cells: Misleading marker gene expression. BMC Neurosci 2009;10:16.
Carleton, A, Petreanu LT, Lansford R et al. Becoming a new neuron in the adult olfactory bulb. Nat Neurosci 2003;6:507–518.
Liu, J, Song L, Jiang C et al. Electrophysiological properties and synaptic function of mesenchymal stem cells during neurogenic differentiation: A mini-review. Int J Artif Organs 2012;35:323–337.
Torrente, Y, Polli E. Mesenchymal stem cell transplantation for neurodegenerative diseases. Cell Transplant 2008;17:1103–1113.
Joyce, N, Annett G, Wirthlin L et al. Mesenchymal stem cells for the treatment of neurodegenerative disease. Regen Med 2010;5: 933–946.
Le Blanc K, Rasmusson I, Sundberg B et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 2004;363:1439–1441.
Sadan, O, Shemesh N, Cohen Y et al. Adult neurotrophic factor-secreting stem cells: A potential novel therapy for neurodegenerative diseases. Isr Med Assoc J 2009;11:201–204.
Caplan, AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem 2006; 98:1076–1084.
Crigler, L, Robey RC, Asawachaicharn A et al. Human mesenchymal stem cell subpopulations express a variety of neuro-regulatory molecules and promote neuronal cell survival and neuritogenesis. Exp Neurol 2006;198:54–64.
Uccelli, A, Benvenuto F, Laroni A et al. Neuroprotective features of mesenchymal stem cells. Best Pract Res Clin Haematol 2011; 24:59–64.
Kan, I, Barhum Y, Melamed E et al. Mesenchymal stem cells stimulate endogenous neurogenesis in the subventricular zone of adult mice. Stem Cell Rev 2011;7:404–412.
Brookmeyer, R, Johnson E, Ziegler-Graham K et al. Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement 2007; 3:186–191.
Kim, JY, Kim DH, Kim JH et al. Soluble intracellular adhesion molecule-1 secreted by human umbilical cord blood-derived mesenchymal stem cell reduces amyloid-beta plaques. Cell Death Differ 2012;19:680–691.
Lee, JK, Jin HK, Endo S et al. Intracerebral transplantation of bone marrow-derived mesenchymal stem cells reduces amyloid-beta deposition and rescues memory deficits in Alzheimer’s disease mice by modulation of immune responses. STEM CELLS 2010;28:329–343.
Lee, HJ, Lee JK, Lee H et al. Human umbilical cord blood-derived mesenchymal stem cells improve neuropathology and cognitive impairment in an Alzheimer’s disease mouse model through modulation of neuroinflammation. Neurobiol Aging 2012;33:588–602.
Lee, JK, Schuchman EH, Jin HK et al. Soluble CCL5 derived from bone marrow-derived mesenchymal stem cells and activated by amyloid beta ameliorates Alzheimer’s disease in mice by recruiting bone marrow-induced microglia immune responses. STEM CELLS 2012;30: 1544–1555.
Kim, S, KA Chang, J Kim et al. The preventive and therapeutic effects of intravenous human adipose-derived stem cells in Alzheimer’s disease mice. PLoS One 2012;7:e45757.
Li, LY, Li JT, Wu QY et al. Transplantation of NGF-gene-modified bone marrow stromal cells into a rat model of Alzheimer’s disease. J Mol Neurosci 2008;34:157–163.
Zhang, P, Zhao G, Kang X et al. Effects of lateral ventricular transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene on cognition in a rat model of Alzheimer’s disease. Neural Regen Res 2012;7:245–250.
Babaei, P, Soltani Tehrani B, Alizadeh A. Transplanted bone marrow mesenchymal stem cells improve memory in rat models of Alzheimer’s disease. Stem Cells Int 2012;2012: 369417.
de Lau LM, Breteler MM. Epidemiology of Parkinson’s disease. Lancet Neurol 2006;5: 525–535.
Nussbaum, RL, Ellis CE. Alzheimer’s disease and Parkinson’s disease. N Engl J Med 2003;348:1356–1364.
Hornykiewicz, O. Biochemical aspects of Parkinson’s disease. Neurology 1998;51(suppl 2):S2–S9.
Lindvall, O, Brundin P, Widner H et al. Grafts of fetal dopamine neurons survive and improve motor function in Parkinson’s disease. Science 1990;247:574–577.
Kordower, JH, Freeman TB, Snow BJ et al. Neuropathological evidence of graft survival and striatal reinnervation after the transplantation of fetal mesencephalic tissue in a patient with Parkinson’s disease. N Engl J Med 1995; 332:1118–1124.
Kordower, JH, Goetz CG, Freeman TB et al. Dopaminergic transplants in patients with Parkinson’s disease: Neuroanatomical correlates of clinical recovery. Exp Neurol 1997;144: 41–46.
Venkataramana, NK, Kumar SK, Balaraju S et al. Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson’s disease. Transl Res 2010;155:62–70.
Venkataramana, NK, Pal R, Rao SA et al. Bilateral transplantation of allogenic adult human bone marrow-derived mesenchymal stem cells into the subventricular zone of Parkinson’s disease: A pilot clinical study. Stem Cells Int 2012;2012:931902.
Fu, YS, Cheng YC, Lin MY et al. Conversion of human umbilical cord mesenchymal stem cells in Wharton’s jelly to dopaminergic neurons in vitro: Potential therapeutic application for Parkinsonism. STEM CELLS 2006;24:115–124.
Wang, J, X Wang, Z Sun et al. Stem cells from human-exfoliated deciduous teeth can differentiate into dopaminergic neuron-like cells. Stem Cells Dev 2010;19:1375–1383.
Khoo, ML, Tao H, Meedeniya AC et al. Transplantation of neuronal-primed human bone marrow mesenchymal stem cells in hemiparkinsonian rodents. PLoS One 2011;6: e19025.
Suon, S, Yang M, Iacovitti L. Adult human bone marrow stromal spheres express neuronal traits in vitro and in a rat model of Parkinson’s disease. Brain Res 2006;1106:46–51.
Levy, YS, Bahat-Stroomza M, Barzilay R et al. Regenerative effect of neural-induced human mesenchymal stromal cells in rat models of Parkinson’s disease. Cytotherapy 2008;10: 340–352.
Offen, D, Barhum Y, Levy YS et al. Intrastriatal transplantation of mouse bone marrow- derived stem cells improves motor behavior in a mouse model of Parkinson’s disease. J Neural Transm Suppl 2007;72:133–143.
Blandini, F, Cova L, Armentero MT et al. Transplantation of undifferentiated human mesenchymal stem cells protects against 6-hydroxydopamine neurotoxicity in the rat. Cell Transplant 2010;19:203–217.
Park, HJ, Shin JY, Lee BR et al. Mesenchymal stem cells augment neurogenesis in the subventricular zone and enhance differentiation of neural precursor cells into dopaminergic neurons in the substantia nigra of a Parkinsonian model. Cell Transplant 2012;21:1629–1640.
Chao, YX, He BP, Tay SS. Mesenchymal stem cell transplantation attenuates blood brain barrier damage and neuroinflammation and protects dopaminergic neurons against MPTP toxicity in the substantia nigra in a model of Parkinson’s disease. J Neuroimmunol 2009; 216:39–50.
Cova, L, Armentero MT, Zennaro E et al. Multiple neurogenic and neurorescue effects of human mesenchymal stem cell after transplantation in an experimental model of Parkinson’s disease. Brain Res 2010;1311:12–27.
Vassos, E, Panas M, Kladi A et al. Effect of CAG repeat length on psychiatric disorders in Huntington’s disease. J Psychiatr Res 2008;42: 544–549.
Landles, C, Bates GP. Huntingtin and the molecular pathogenesis of Huntington’s disease. Fourth in molecular medicine review series. EMBO Rep 2004;5:958–963.
Bachoud-Lévi AC, Gaura V, Brugieres P et al. Effect of fetal neural transplants in patients with Huntington’s disease 6 years after surgery: A long-term follow-up study. Lancet Neurol 2006;5:303–309.
Bachoud-Lévi AC, Remy P, Nguyen JP et al. Motor and cognitive improvements in patients with Huntington’s disease after neural transplantation. Lancet 2000;356:1975–1979.
Lin, YT, Chern Y, Shen CK et al. Human mesenchymal stem cells prolong survival and ameliorate motor deficit through trophic support in Huntington’s disease mouse models. PLoS One 2011;6:e22924.
Snyder, BR, Chiu AM, Prockop DJ et al. Human multipotent stromal cells (MSCs) increase neurogenesis and decrease atrophy of the striatum in a transgenic mouse model for Huntington’s disease. PLoS One 2010;5:e9347.
Rossignol, J, Boyer C, Leveque X et al. Mesenchymal stem cell transplantation and DMEM administration in a 3NP rat model of Huntington’s disease: Morphological and behavioral outcomes. Behav Brain Res 2011;217: 369–378.
Dey, ND, Bombard MC, Roland BP et al. Genetically engineered mesenchymal stem cells reduce behavioral deficits in the YAC 128 mouse model of Huntington’s disease. Behav Brain Res 2010;214:193–200.
Sadan, O, Shemesh N, Barzilay R et al. Mesenchymal stem cells induced to secrete neurotrophic factors attenuate quinolinic acid toxicity: A potential therapy for Huntington’s disease. Exp Neurol 2012;234:417–427.
Ronaghi, M, Erceg S, Moreno-Manzano V et al. Challenges of stem cell therapy for spinal cord injury: Human embryonic stem cells, endogenous neural stem cells, or induced pluripotent stem cells? Stem Cells 2010;28:93–99.
Karamouzian, S, Nematollahi-Mahani SN, Nakhaee N et al. Clinical safety and primary efficacy of bone marrow mesenchymal cell transplantation in subacute spinal cord injured patients. Clin Neurol Neurosurg 2012;114: 935–939.
Sieber-Blum M, Schnell L, Grim M et al. Characterization of epidermal neural crest stem cell (EPI-NCSC) grafts in the lesioned spinal cord. Mol Cell Neurosci 2006;32:67–81.
Alexanian, AR, Fehlings MG, Zhang Z et al. Transplanted neurally modified bone marrow- derived mesenchymal stem cells promote tissue protection and locomotor recovery in spinal cord injured rats. Neurorehabil Neural Repair 2011;25:873–880.
Pedram, MS, Dehghan MM, Soleimani M et al. Transplantation of a combination of autologous neural differentiated and undifferentiated mesenchymal stem cells into injured spinal cord of rats. Spinal Cord 2010;48:457–463.
Zhang, W, Yan Q, Zeng YS et al. Implantation of adult bone marrow-derived mesenchymal stem cells transfected with the neurotrophin- 3 gene and pretreated with retinoic acid in completely transected spinal cord. Brain Res 2010;1359:256–271.
Schira, J, Gasis M, Estrada V et al. Significant clinical, neuropathological and behavioural recovery from acute spinal cord trauma by transplantation of a well-defined somatic stem cell from human umbilical cord blood. Brain 2012;135:431–446.
Park, SI, Lim JY, Jeong CH et al. Human umbilical cord blood-derived mesenchymal stem cell therapy promotes functional recovery of contused rat spinal cord through enhancement of endogenous cell proliferation and oligogenesis. J Biomed Biotechnol 2012; 2012:362473.
Sasaki, M, Radtke C, TanAMet al. BDNFhypersecreting human mesenchymal stem cells promote functional recovery, axonal sprouting, and protection of corticospinal neurons after spinal cord injury. J Neurosci 2009; 29:14932–14941.
Quertainmont, R, Cantinieaux D, Botman O et al. Mesenchymal stem cell graft improves recovery after spinal cord injury in adult rats through neurotrophic and pro-angiogenic actions. PLoS One 2012;7:e39500.
Biernaskie, J, Sparling JS, Liu J et al. Skinderived precursors generate myelinating Schwann cells that promote remyelination and functional recovery after contusion spinal cord injury. J Neurosci 2007;27:9545–9559.
Kamada, T, Koda M, Dezawa M et al. Transplantation of human bone marrow stromal cell-derived Schwann cells reduces cystic cavity and promotes functional recovery after contusion injury of adult rat spinal cord. Neuropathology 2011;31:48–58.
Xu, X, Geremia N, Bao F et al. Schwann cell coculture improves the therapeutic effect of bone marrow stromal cells on recovery in spinal cord-injured mice. Cell Transplant 2011; 20:1065–1086.
Karussis, D, Karageorgiou C, Vaknin ADembinsky et al. Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol 2010;67:1187–1194.
Mazzini, L, Ferrero I, Luparello V et al. Mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: A Phase I clinical trial. Exp Neurol 2010;223:229–237.
Kaspar, BK, Mesenchymal stem cells as trojan horses for GDNF delivery in ALS. Mol Ther 2008;16:1905–1906.
Suzuki, M, McHugh J, Tork C et al. Direct muscle delivery of GDNF with human mesenchymal stem cells improves motor neuron survival and function in a rat model of familial ALS. Mol Ther 2008;16:2002–2010.
Vercelli, A, Mereuta OM, Garbossa D et al. Human mesenchymal stem cell transplantation extends survival, improves motor performance and decreases neuroinflammation in mouse model of amyotrophic lateral sclerosis. Neurobiol Dis 2008;31:395–405.
Uccelli, A, Milanese M, Principato MC et al. Intravenous mesenchymal stem cells improve survival and motor function in experimental amyotrophic lateral sclerosis. Mol Med 2012;18:794–804.
Knippenberg, S, Thau N, Dengler R et al. Intracerebroventricular injection of encapsulated human mesenchymal cells producing glucagon- like peptide 1 prolongs survival in a mouse model of ALS. PLoS One 2012;7:e36857.
Boucherie, C, Caumont AS, Maloteaux JM et al. In vitro evidence for impaired neuroprotective capacities of adult mesenchymal stem cells derived from a rat model of familial amyotrophic lateral sclerosis (hSOD1(G93A)). Exp Neurol 2008;212:557–561.
Koh, SH, Baik W, Noh MY et al. The functional deficiency of bone marrow mesenchymal stromal cells in ALS patients is proportional to disease progression rate. Exp Neurol 2012; 233:472–480.
Cho, GW, Noh MY, Kim HY et al. Bone marrow-derived stromal cells from amyotrophic lateral sclerosis patients have diminished stem cell capacity. Stem Cells Dev 2010;19: 1035–1042.
Choi, MR, Kim HY, Park JY et al. Selection of optimal passage of bone marrow-derived mesenchymal stem cells for stem cell therapy in patients with amyotrophic lateral sclerosis. Neurosci Lett 2010;472:94–98.
Kim, H, Kim HY, Choi MR et al. Dosedependent efficacy of ALS-human mesenchymal stem cells transplantation into cisterna magna in SOD1–G93A ALS mice. Neurosci Lett 2010;468:190–194.
Donnan, GA, Fisher M, MacleodMet al. Stroke. Lancet 2008;371:1612–1623.
Bang, OY, Lee JS, Lee PH et al. Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol 2005;57:874–882.
Bhasin, A, Padma Srivastava MV, Mohanty S et al. Stem cell therapy: A clinical trial of stroke. Clin Neurol Neurosurg (in press).
Honmou, O, Houkin K, Matsunaga T et al. Intravenous administration of auto serumexpanded autologous mesenchymal stem cells in stroke. Brain 2011;134:1790–1807.
Lee, JS, Hong JM, Moon GJ et al. A longterm follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke. STEM CELLS 2010; 28:1099–1106.
Mora-Lee S, Sirerol-Piquer MS, Gutierrez- Perez M et al. Therapeutic effects of hMAPC and hMSC transplantation after stroke in mice. PLoS One 2012;7:e43683.
Fatar, M, Stroick M, Griebe M et al. Lipoaspirate- derived adult mesenchymal stem cells improve functional outcome during intracerebral hemorrhage by proliferation of endogenous progenitor cells stem cells in intracerebral hemorrhages. Neurosci Lett 2008;443: 174–178.
Leong, WK, Henshall TL, Arthur A et al. Human adult dental pulp stem cells enhance poststroke functional recovery through nonneural replacement mechanisms. STEM CELLS TRANSL MED 2012;1:177–187.
Liu, N, Zhang Y, Fan L et al. Effects of transplantation with bone marrow-derived mesenchymal stem cells modified by Survivin on experimental stroke in rats. J Transl Med 2011;9:105.
Wakabayashi, K, Nagai A, Sheikh AM et al. Transplantation of human mesenchymal stem cells promotes functional improvement and increased expression of neurotrophic factors in a rat focal cerebral ischemia model. J Neurosci Res 2010;88:1017–1025.
Lin, YC, Ko TL, Shih YH et al. Human umbilical mesenchymal stem cells promote recovery after ischemic stroke. Stroke 2011;42: 2045–2053.
Kurozumi, K, Nakamura K, Tamiya T et al. Mesenchymal stem cells that produce neurotrophic factors reduce ischemic damage in the rat middle cerebral artery occlusion model. Mol Ther 2005;11:96–104.
Yang, C, Zhou L, Gao X et al. Neuroprotective effects of bone marrow stem cells overexpressing glial cell line-derived neurotrophic factor on rats with intracerebral hemorrhage and neurons exposed to hypoxia/reoxygenation. Neurosurgery 2011;68:691–704.
Yang, KL, Lee JT, Pang CY et al. Human adipose-derived stem cells for the treatment of intracerebral hemorrhage in rats via femoral intravenous injection. Cell Mol Biol Lett 2012; 17:376–392.
Lim, JY, Jeong CH, Jun JA et al. Therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells after intrathecal administration by lumbar puncture in a rat model of cerebral ischemia. Stem Cell Res Ther 2011;2:38.
Tsai, LK, Wang Z, Munasinghe J et al. Mesenchymal stem cells primed with valproate and lithium robustly migrate to infarcted regions and facilitate recovery in a stroke model. Stroke 2011;42:2932–2939.
Steiner, B, Roch M, Holtkamp N et al. Systemically administered human bone marrow- derived mesenchymal stem home into peripheral organs but do not induce neuroprotective effects in the MCAo-mouse model for cerebral ischemia. Neurosci Lett 2012;513:25–30.
Freedman, MS, Bar-Or A, Atkins HL et al. The therapeutic potential of mesenchymal stem cell transplantation as a treatment for multiple sclerosis: Consensus report of the International MSCT Study Group. Mult Scler 2010;16:503–510.
Mallam, E, Kemp K, Wilkins A et al. Characterization of in vitro expanded bone marrow- derived mesenchymal stem cells from patients with multiple sclerosis. Mult Scler 2010; 16:909–918.
Connick, P, Kolappan M, Crawley C et al. Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: An open-label phase 2a proof-of-concept study. Lancet Neurol 2012;11:150–156.
Yamout, B, Hourani R, Salti H et al. Bone marrow mesenchymal stem cell transplantation in patients with multiple sclerosis: A pilot study. J Neuroimmunol 2010;227: 185–189.
Gerdoni, E, Gallo B, Casazza S et al. Mesenchymal stem cells effectively modulate pathogenic immune response in experimental autoimmune encephalomyelitis. Ann Neurol 2007;61:219–227.
Kassis, I, Grigoriadis N, Gowda-Kurkalli B et al. Neuroprotection and immunomodulation with mesenchymal stem cells in chronic experimental autoimmune encephalomyelitis. Arch Neurol 2008;65:753–761.
Zhang, J, Li Y, Chen J et al. Human bone marrow stromal cell treatment improves neurological functional recovery in EAE mice. Exp Neurol 2005;195:16–26.
Liu, R, Zhang Z, Lu Z et al. Human umbilical cord stem cells ameliorate experimental autoimmune encephalomyelitis by regulating immunoinflammation and remyelination. Stem Cells Dev 2012 (in press).
Zhang, J, Li Y, Lu M et al. Bone marrow stromal cells reduce axonal loss in experimental autoimmune encephalomyelitis mice. J Neurosci Res 2006;84:587–595.
Harris, VK, Yan QJ, Vyshkina T et al. Clinical and pathological effects of intrathecal injection of mesenchymal stem cell-derived neural progenitors in an experimental model of multiple sclerosis. J Neurol Sci 2012;313:167–177.
Bai, L, Lennon DP, Eaton V et al. Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis. Glia 2009;57:1192–1203.
Bai, L, Lennon DP, Caplan AI et al. Hepatocyte growth factor mediates mesenchymal stem cell-induced recovery in multiple sclerosis models. Nat Neurosci 2012;15:862–870.
Uccelli, A, Morando S, Bonanno S et al. Mesenchymal stem cells for multiple sclerosis: Does neural differentiation really matter? Curr Stem Cell Res Ther 2011;6:69–72.
Uccelli, A, Laroni A, Freedman MS. Mesenchymal stem cells for the treatment of multiple sclerosis and other neurological diseases. Lancet Neurol 2011;10:649–656.